The invention relates to the production of hexahydro-iso-alpha-acids, which are reduced derivatives of iso-alpha-acids, useful to impart bitterness and foam to beer. These hexahydro-iso-alpha-acids are bitter hop acid derivatives with excellent foam-stabilizing properties, and preferable to all other iso-alpha-acid products in terms of resistance to photolytic and oxidative degradation (U.S. Pat. No. 3,552,975).
Traditionally, the bitter beer flavor derives from the alpha-acids present in hop cones. During the wort boiling stage of the conventional brewing process, the alpha-acids are extracted from the (powdered) hop cones and partly converted to the corresponding bitter iso-alpha-acids. However, the hop utilization (or the iso-alpha-acid yield) in the traditional brewing process is only about 35% (GB 1,158,697).
It became clear that the hop utilization can be improved by performing the alpha-acid isomerisation outside the brewing process and more specifically by off-line pre-isomerising the alpha-acids under the effect of inorganic basic compounds (U.S. Pat. No. 3,962,061; U.S. Pat. No. 4,002,683; U.S. Pat. No. 4,758,445; U.S. Pat. No. 5,015,491; U.S. Pat. No. 5,155,276; U.S. Pat. No. 5,370,897). The use of such off-line produced iso-alpha-acids improves the utilization of the hop alpha-acids in the brewing process to about 70% at most.
The iso-alpha-acids have however a number of intrinsic disadvantages. One such negative property is their sensitivity to photolytic degradation which leads to the development of the so-called ‘lightstruck flavor’ which is ascribed to the formation of 3-methyl-2-butene-1-thiol (MBT), also called ‘skunky thiol’. The occurrence of the photolytic reaction is a consequence of the presence of an iso-3-hexenoyl side chain in the iso-alpha-acid molecules. By modifying the molecular structure of the iso-alpha-acids, for example by reducing the C═C and/or C═O bonds in this iso-3-hexenoyl side chain, substantial MBT by-product formation, e.g. in beer, as a consequence of photolytic degradation can be prevented.
Consequently, reduced iso-alpha-acid derivatives have been introduced, to say dihydro-iso-alpha-acids, tetrahydro-iso-alpha-acids and hexahydro-iso-alpha-acids, and are now used by many brewers, generally by their addition after the primary fermentation stage of the brewing process. The dihydro-iso-alpha-acids (also called rho-iso-alpha-acids) are obtained by the reduction of the carbonyl group in the aforementioned iso-3-hexenoyl chain to a hydroxyl group, generally using alkali metal borohydride as the reducing agent. The tetrahydro-iso-alpha-acids are obtained via hydrogenation of the C═C bonds in the aforementioned iso-3-hexenoyl side chain and the isopentenyl side chain. The hexahydro-iso-alpha-acids are produced by combining the aforementioned reduction and hydrogenation processes.
All industrially applied procedures for the production of dihydro-iso-alpha-acids use a borohydride based reduction of iso-alpha-acids (U.S. Pat. No. 3,558,326; U.S. Pat. No. 4,324,810). The industrial processes for the production of tetrahydro-iso-alpha-acids generally apply heterogeneous Pd based catalysts (U.S. Pat. No. 5,013,571; U.S. Pat. No. 5,600,012).
For the formation of hexahydro-iso-alpha-acids two approaches have been described. The first type uses tetrahydro-iso-alpha-acids as the precursor and the desired hexahydro-iso-alpha-acids are obtained by a reduction using an alkali metal borohydride (U.S. Pat. No. 3,552,975). A second approach starts from dihydro-iso-alpha-acids, which are hydrogenated with hydrogen gas over a supported Pd catalyst (U.S. Pat. No. 5,013,571).
U.S. Pat. No. 3,552,975 describes the formation of the ‘skunk-proof’ hexahydro-iso-alpha-acids starting from tetrahydro-iso-alpha-acids, by using an alkali metal borohydride as the reducing agent, water and/or alcohol solvents as preferred inert protic reaction media, and mild alkaline pH conditions. After the reduction process, the excess reductant is decomposed by adding an aqueous HCl solution, and the hexahydro-iso-alpha-acids are recovered via extraction with a water-immiscible solvent (e.g. lower hydrocarbons or ethers). To obtain the hexahydro-iso-alpha-acid product in high purity, an additional solvent evaporation step is required.
U.S. Pat. No. 6,198,004 describes a process for converting iso-alpha-acids to tetrahydro-iso-alpha-acids by means of incremental or continuous addition to the reaction mixture of noble metal catalysts, preferably Pd catalysts, that catalyze the hydrogenation of the iso-alpha-acids towards tetrahydro-iso-alpha-acids, as supported by Pd catalyst based experimental data. However, U.S. Pat. No. 6,198,004 also teaches that when hexahydro-iso-alpha-acids are the desired products, the tetrahydro-iso-alpha-acid needs to be further reduced in a reduction step, that particularly employs a reducing agent of the alkali metal borohydride type.
U.S. Pat. No. 5,013,571 describes the reduction of iso-alpha-acids to dihydro-iso-alpha-acids with alkali metal borohydride compounds and the subsequent hydrogenation to hexahydro-iso-alpha-acids over Pd catalysts, with carbon, barium carbonate, barium sulphate, calcium carbonate or alumina as the supporting material. This patent also reflects the critical nature of these reduction and hydrogenation processes, by reporting side chain cleavage, during the reduction process as a consequence of the alkaline pH conditions, and during the hydrogenation process resulting from hydrogenolysis.
Approaches to avoid these perhydrogenation products are described in U.S. Pat. No. 5,600,012. If undesired side products resulting from hydrogenolytic degradation are present in the product, an additional extraction step using e.g. hexane is required to remove these degradation products followed by a solvent evaporation step to obtain the purified hexahydro-iso-alpha-acids.
U.S. Pat. No. 7,344,746 describes the production of hexahydro-iso-alpha-acids from dihydro-iso-alpha-acids via a (solvent-free) hydrogenation process using Pd and Pt based catalysts, with possible admixing of carbon dioxide, which can be performed in batch or continuous mode.
The above clearly shows that the transformation of hop iso-alpha-acids to hexahydro-iso-alpha-acids known in the art requires complex multistep processes, comprising hydrogenation and (alkali metal borohydride based) reduction reactions, with often the unwanted formation of degradation by-products (e.g. side chain cleavage and hydrogenolysis) that need to be removed by means of extraction and evaporation processes. Thus, there remains a need for improved, simplified methods to obtain hexahydro-iso-alpha-acids from iso-alpha-acids or tetrahydro-iso-alpha-acids.